6-31508317-A-G

Variant names:

• chr6-31508317-A-G
• rs3131636
• NM_005931.5:c.1024+786A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005931.5(MICB):​c.1024+786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,132 control chromosomes in the GnomAD database, including 45,690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45690 hom., cov: 32)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 7 publications found

Genes affected

MICB (HGNC:7091): (MHC class I polypeptide-related sequence B) This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005931.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	NM_005931.5	MANE Select	c.1024+786A>G		intron	N/A	NP_005922.2	A0A7D9H7X8
	MICB	NM_001289160.2		c.928+786A>G		intron	N/A	NP_001276089.1	F5H7Q8
	MICB	NM_001289161.2		c.895+786A>G		intron	N/A	NP_001276090.1	Q29980-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	ENST00000252229.7	TSL:1 MANE Select	c.1024+786A>G		intron	N/A	ENSP00000252229.6	Q29980-1
	MICB	ENST00000399150.7	TSL:1	c.895+786A>G		intron	N/A	ENSP00000382103.3	Q29980-2
	MICB	ENST00000538442.5	TSL:2	c.928+786A>G		intron	N/A	ENSP00000442345.1	F5H7Q8

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117488 AN: 152014 Hom.: 45648 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.789

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.773 AC: 117582 AN: 152132 Hom.: 45690 Cov.: 32 AF XY: 0.771 AC XY: 57370 AN XY: 74384

African (AFR) AF: 0.811 AC: 33659 AN: 41478

American (AMR) AF: 0.814 AC: 12444 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3121 AN: 3472

East Asian (EAS) AF: 0.882 AC: 4566 AN: 5178

South Asian (SAS) AF: 0.835 AC: 4030 AN: 4826

European-Finnish (FIN) AF: 0.658 AC: 6969 AN: 10590

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50317 AN: 67984

Other (OTH) AF: 0.790 AC: 1669 AN: 2112

Alfa AF: 0.761 Hom.: 5739

Bravo AF: 0.787

Asia WGS AF: 0.803 AC: 2790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.58
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3131636; hg19: chr6-31476094;